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Scientific article
English

Magnesium sensing via LFA-1 regulates CD8+ T cell effector function

Published inCell, vol. 185, no. 4, p. 585-602.e29
Publication date2022-02-17
First online date2022-01-13
Abstract

The relevance of extracellular magnesium in cellular immunity remains largely unknown. Here, we show that the co-stimulatory cell-surface molecule LFA-1 requires magnesium to adopt its active conformation on CD8+T cells, thereby augmenting calcium flux, signal transduction, metabolic reprogramming, immune synapse formation, and, as a consequence, specific cytotoxicity. Accordingly, magnesium-sufficiency sensed via LFA-1 translated to the superior performance of pathogen- and tumor-specific T cells, enhanced effectiveness of bi-specific T cell engaging antibodies, and improved CAR T cell function. Clinically, low serum magnesium levels were associated with more rapid disease progression and shorter overall survival in CAR T cell and immune checkpoint antibody-treated patients. LFA-1 thus directly incorporates information on the composition of the microenvironment as a determinant of outside-in signaling activity. These findings conceptually link co-stimulation and nutrient sensing and point to the magnesium-LFA-1 axis as a therapeutically amenable biologic system.

eng
Keywords
  • CAR T cells
  • Mg2+
  • T cell engaging antibodies
  • Co-stimulation/LFA-1
  • Immune control
  • Integration of microenvironment and T cell function
  • Magnesium
  • Memory CD8 T cells
  • Microenvironment
  • Tumor-specific T cells
Citation (ISO format)
LÖTSCHER, Jonas et al. Magnesium sensing via LFA-1 regulates CD8<sup>+</sup> T&nbsp;cell effector function. In: Cell, 2022, vol. 185, n° 4, p. 585–602.e29. doi: 10.1016/j.cell.2021.12.039
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Identifiers
ISSN of the journal0092-8674
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Creation01/25/2022 1:49:00 PM
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